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Determination of phenothiazines in human body fluids by solid‐phase microextraction and liquid chromatography/tandem mass spectrometry
Author(s) -
Kumazawa Takeshi,
Seno Hiroshi,
WatanabeSuzuki Kanako,
Hattori Hideki,
Ishii Akira,
Sato Keizo,
Suzuki Osamu
Publication year - 2000
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/1096-9888(200009)35:9<1091::aid-jms31>3.0.co;2-m
Subject(s) - chemistry , chromatography , phenothiazine , mass spectrometry , tandem mass spectrometry , solid phase microextraction , urine , electrospray ionization , detection limit , selected ion monitoring , gas chromatography–mass spectrometry , medicine , biochemistry , pharmacology
Eleven phenothiazine derivatives with heavy side‐chains were found to be extractable from human whole blood and urine samples by solid‐phase microextraction (SPME) with a polyacrylate‐coated fiber. The fiber was then injected into the desorption chamber of an SPME–liquid chromatography (LC) interface for LC/tandem mass spectrometry (MS/MS) with positive ion electrospray (ES) ionization. All compounds formed base peaks due to [M + 1] + ions by LC/ES‐MS/MS. By use of LC/ES‐MS/MS, the product ions produced from each [M + 1] + ion showed base peaks due to side‐chain liberation. Selected reaction monitoring (SRM) and selected ion monitoring (SIM) were compared for the detection of the 11 phenothiazine derivatives from human whole blood and urine. SRM showed much higher sensitivity than SIM for both types of sample. Therefore, a detailed procedure for the detection of drugs by SRM with SPME‐LC/MS/MS was established and carefully validated. The extraction efficiencies of the 11 phenothiazine derivatives spiked into whole blood and urine were 0.0002–0.12 and 2.6–39.8%, respectively. The regression equations for the 11 phenothiazine derivatives showed excellent linearity with detection limits of 0.2–200 ng ml −1 for whole blood and 4–22 pg ml −1 for urine. The intra‐ and inter‐day precisions for whole blood and urine samples were not greater than 15.1%. The data obtained after oral administration of perazine or flupentixol to a male subject are presented. Copyright © 2000 John Wiley & Sons, Ltd.